The purpose of this study was to prepare prednisolone pH-dependent release tablets and evaluate their advantages as a colon targeted drug delivery system. prednisolone insoluble in water and unstable in gastric environment was formulated into pH-dependent tablets coated with combinations of two methacrylic acid copolymers Eudragit L100 and Eudragit S100. The influence of core tablet compositions, polymer combination ratios and coating levels on the in vitro release rate of prednisolone from coated tablets was investigated. The results showed that less than 10% drug was released in 0.1 N HCl within 2 hr, and about 90% of the drug was released in the pH 7.2 phosphate buffer within 6 hr. Colon drug delivery is advantageous in the treatment of colonic disease and oral delivery of drugs unstable or susceptible to enzymatic degradation in upper GI tract. In this study coated tablets that is resistant to gastric and small intestinal pH conditions but can be easily dissolved in colonic pH. The results of the present study have demonstrated that the pH-dependent tablet system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of prednisolone for the treatment of ulcerative colitis.